In order to gain a greater understanding of the neural mechanisms that mediate human cognitive function new approaches and technologies are needed to dramatically expand the ability to record and manipulate the activity of large numbers of neurons throughout widespread areas of the primate brain. Over the past 5-10 years, our groups have made two major advances in the study of neural circuits in non-human primates. We have developed and refined new methods for the large-scale recording of neuronal activity in behaving monkeys and commercially disseminated these technologies to laboratories throughout North America, Europe and Asia (Goodell and Gray). We have also implemented state-of-the-art methods for manipulating activity in neural circuits in behaving monkeys using a combination of optogenetics and electrophysiology (Sheinberg and Pesaran). Now we seek to refine, optimize and combine these technologies to expand their scope, reliability and efficiency, and accelerate their development and dissemination to the wider neuroscientific community. The first specific aim is to refine and optimize a microdrive system for the long-term implantation and independent control of hundreds of microelectrodes capable of recording neuronal activity from any region throughout the depth of the brain in behaving non-human primates. The second specific aim is to develop and refine a microdrive system that enables the optogenetic control and electrophysiological measurement of neuronal activity from large numbers of independently movable optrodes capable of targeting any region throughout the depth of the brain in behaving non-human primates. To accomplish these objectives, we will conduct two lines of closely coordinated design, development and research efforts to dramatically improve the capability of the current technology and to rigorously test the instruments in awake, behaving monkeys in two separate laboratories. The resulting technology will enable researchers to manipulate and measure spatiotemporal patterns of activity in large-scale circuits in behaving monkeys and thereby test hypotheses of neural circuit function that are well beyond the scope of existing methods.